Abstract
BackgroundSome organic chemicals are known to cause allergic disorders such as bronchial asthma and hypersensitivity pneumonitis, and it has been considered that they do not cause irreversible pulmonary fibrosis. It has recently been reported, however, that cross-linked acrylic acid-based polymer, an organic chemical, might cause serious interstitial lung diseases, including pulmonary fibrosis. We investigated whether or not intratracheal instillation exposure to cross-linked polyacrylic acid (CL-PAA) can cause lung disorder in rats.MethodsMale F344 rats were intratracheally instilled with dispersed CL-PAA at low (0.2 mg/rat) and high (1.0 mg/rat) doses, and were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure to examine inflammatory and fibrotic responses and related gene expressions in the lungs. Rat lungs exposed to crystalline silica, asbestos (chrysotile), and NiO and CeO2 nanoparticles were used as comparators.ResultsPersistent increases in total cell count, neutrophil count and neutrophil percentage, and in the concentration of the cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 and C-X-C motif chemokine 5 (CXCL5), which correlated with lung tissue gene expression, were observed in bronchoalveolar lavage fluid (BALF) from 3 days until at least 1 month following CL-PAA intratracheal instillation. Persistent increases in heme oxygenase-1 (HO-1) in the lung tissue were also observed from 3 days to 6 months after exposure. Histopathological findings of the lungs demonstrated that extensive inflammation at 3 days was greater than that in exposure to silica, NiO nanoparticles and CeO2 nanoparticles, and equal to or greater than that in asbestos (chrysotile) exposure, and the inflammation continued until 1 month. Fibrotic changes also progressed after 1 month postexposure.ConclusionOur results suggested that CL-PAA potentially causes strong neutrophil inflammation in the rat and human lung.
Highlights
Some organic chemicals are known to cause allergic disorders such as bronchial asthma and hypersen‐ sitivity pneumonitis, and it has been considered that they do not cause irreversible pulmonary fibrosis
Characterization of CL‐Polyacrylic acid (PAA) The fundamental characteristics of cross-linked polyacrylic acid (CL-PAA) are summarized in Tables 1 and 2
Intratracheal instillation of nickel oxide (NiO) and C eO2 nanoparticles under the same exposure dose as in the present study showed an increase in cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2 concentrations in bronchoalveolar lavage fluid (BALF) [16, 17, 29], and the level of increase due to CL-PAA exposure was almost the same (Additional file 2: Figure S1A, B)
Summary
Some organic chemicals are known to cause allergic disorders such as bronchial asthma and hypersen‐ sitivity pneumonitis, and it has been considered that they do not cause irreversible pulmonary fibrosis It has recently been reported, that cross-linked acrylic acid-based polymer, an organic chemical, might cause serious inter‐ stitial lung diseases, including pulmonary fibrosis. We investigated whether or not intratracheal instillation exposure to cross-linked polyacrylic acid (CL-PAA) can cause lung disorder in rats Inorganic chemicals such as asbestos and crystalline silica are known to cause irreversible interstitial pulmonary fibrotic lesions such as pneumoconiosis. Occupational and environmental exposure to organic chemicals (e.g., exposure to wood dust, livestock and vegetable dust/animal dust) has been identified as a potential risk factor for developing irreversible pulmonary fibrosis with very poor prognosis (5-year survival rate of 20 to 30%) [3]. According to the dust concentration by the researchers who investigated there, the maximum personal exposure concentration of respirable dust was 2.1 mg/m3 (7.8 mg/m3 as inhalable dust) at 8 h-Time Weighted Average (8 h-TWA), and the personal exposure concentration was high in the extreme, especially in the work of adding CL-PAA-based to the hopper (41.8 mg/ m3 as inhalable dust)
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